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Risk of colon cancer in hereditary non-polyposis colorectal cancer patients as predicted by fuzzy modeling:Influence of smoking

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World Journal of Gastroenterology 2006年第28期12卷 4485-4491页

作者： Rhonda M Brand david d jones Henry T Lynch Randall E Brand Patrice Watson Ramesh Ashwathnayaran Hemant K Roy department of Internal Medicine Evanston Northwestern Healthcare and Feinberg School of Medicine at Northwestern UniversityEvanston ILUinted States department of Biological Systems Engineering University of Nebraska-LincolnLincoln NEUinted States Hereditary Cancer Institute Creighton UniversityUinted States

AIM： To investigate whether a fuzzy logic model could predict colorectal cancer （CRC） risk engendered by smoking in hereditary non-polyposis colorectal cancer （HNPCC） patients. METHOdS： Three hundred and forty HNPCC mismatch repair （MMR） mutation carriers from the Creighton University Hereditary Cancer Institute Registry were selected for modeling. Age-dependent curves were generated to elucidate the joint effects between gene mutation （hMLH1 or hMSH2）, gender, and smoking status on the probability of developing CRC. RESULTS： Smoking significantly increased CRC risk in male hMSH2 mutation carriers （P 〈 0.05）. hMLH1 mutations augmented CRC risk relative to hMSH2 mutation carriers for males （P 〈 0.05）. Males had a significantly higher risk of CRC than females for hMLH1 non smokers （P 〈 0.05）, hMLH1 smokers （P 〈 0.1） and hMSH2 smokers （P 〈 0.1）. Smoking promoted CRC in a dose-dependent manner in hMSH2 in males （P 〈 0.05）. Females with hMSH2 mutations and both sexes with the hMLH1 groups only demonstrated a smoking effect after an extensive smoking history （P 〈 0.05）. CONCLUSION： CRC promotion by smoking in HNPCC patients is dependent on gene mutation, gender and age. These data demonstrate that fuzzy modeling may enable formulation of clinical risk scores, thereby allowing individualization of CRC prevention strategies.

关键词： Hereditary non-polyposis colorectal cancer Lynch syndrome Smoking Colorectal cancer Fuzzy modeling Risk assessment

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Relating estimates of wood properties of birch to stem form, age and species

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Journal of Forestry Research 2024年第3期35卷 1-11页

作者： Grace jones Maria Ulan Mateusz Liziniewicz Johan Lindeberg Stergios Adamopoulos Teagasc Forestry development department Ashtown Research CentreDublin 15 D15DY05Ireland Research Institutes of Sweden(RISE) GoteborgSweden The Forest Research Institute of Sweden(Skogforsk) Ekebo 225026890SvalovSweden department of Forestry and Wood Technology Linnaeus University35195VaxjoSweden department of Forest Biomaterials and Technology Swedish University of Agricultural SciencesBox 700875007 UppsalaSweden

Birch has long suffered from a lack of active forest management,leading many researchers to use mate-rial without a detailed management *** collected from three birch(Betula pendula Roth,*** Ehrh.)sites in southern Sweden were analyzed using regression analysis to detect any trends or differences in wood proper-ties that could be explained by stand history,tree age and stem *** sites were genetics trials established in the same *** of acoustic velocity(AV)from non-destructive testing(NdT)and predicted AV had a higher correlation if data was pooled across sites and other stem form factors were considered.A subsample of stems had radial profiles of X-ray wood density and ring width by year created,and wood density was related to ring number from the pith and ring *** seemed likely that wood density was negatively related to ring width for both birch *** models had slight improvements if site and species were included,but only the youngest site with trees at age 15 had both birch *** paper indicated that NdT values need to be considered separately,and any predictive models will likely be improved if they are specific to the site and birch species measured.

关键词： Acoustic velocity Non-destructive testing Predictive models Regression analysis Wood density

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There is more to the knee joint than just the quadriceps:A systematic review with meta-analysis and evidence gap map of hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders

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Journal of Sport and Health Science 2024年第4期13卷 521-536页

作者： Helder S.Lopes Marina C.Waiteman Liliam B.Priore Neal R.Glaviano david M.Bazett-jones Ronaldo V.Briani Fabio M.Azevedo School of Science and Technology Physical Therapy DepartmentSao Paulo State University(UNESP)Presidente Prudente 19060-900Brazil department of Kinesiology College of AgricultureHealth and Natural ResourcesUniversity of ConnecticutStorrsCT 06269USA School of Exercise and Rehabilitation Sciences College of Health and Human ServicesUniversity of ToledoToledoOH 43606USA

Background:Impairments in hamstring strength,flexibility,and morphology have been associated with altered knee biomechanics,pain,and *** the presence of these impairments in individuals with gradual-onset knee disorders is important and may indicate targets for assessment and *** systematic review aimed to synthesize the literature to determine the presence of impairments in hamstring strength,flexibility,and morphology in individuals with gradual-onset knee ***:Five databases(MEdLINE,Embase,CINAHL,SPORTdiscus,and Web of Science)were searched from inception to September *** studies comparing hamstring outcomes(e.g.,strength,flexibility,and/or morphology)between individuals with gradual-onset knee disorders and their unaffected limbs or pain-free controls were ***-analyses for each knee disorder were ***-level certainty was assessed using the Grading of Recommendations Assessment,development,and Evaluation,and evidence gap maps were ***:Seventy-nine studies across 4 different gradual-onset knee disorders(i.e.,knee osteoarthritis(OA),patellofemoral pain(PFP),chondromalacia patellae,and patellar tendinopathy)were *** with knee OA presented with reduced hamstring strength compared to pain-free controls during isometric(standard mean difference(SMd)=-0.76,95%confidence interval(95%CI):-1.32 to-0.21)and concentric contractions(SMd=-0.97,95%CI:-1.49 to-0.45).Individuals with PFP presented with reduced hamstring strength compared to painfree controls during isometric(SMd=-0.48,95%CI:-0.82 to-0.14),concentric(SMd=-1.07,95%CI:-2.08 to-0.06),and eccentric contractions(SMd=-0.59,95%CI:-0.97 to-0.21).No differences were observed in individuals with patellar *** with PFP presented with reduced hamstring flexibility when compared to pain-free controls(SMd=-0.76,95%CI:-1.15 to-0.36).Evidence gap maps identified insufficient evidence for chondromalacia patel

关键词： Chondromalacia patellae Knee flexors Knee osteoarthritis Patellar tendinopathy Patellofemoral pain

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Breaking paradigms: Long non-coding RNAs forming gene fusions with potential implications in cancer

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Genes & diseases 2024年第3期11卷 311-323页

作者： david Sanchez-Marin Macrina Beatriz Silva-Cazares Fany Iris Porras-Reyes Rebeca Garcia-Roman Alma d.Campos-Parra Posgrado en Ciencias Biologicas Facultad de MedicinaUniversidad Nacional Autonoma de MexicoCiudad de MexicoC.P.04360Mexico Unidad Academica Multidisciplinaria Region Altiplano Universidad Autonoma de San Luis Potost(UASLP)Carretera a Cedral Km 5+600Ejido San Jose de la TrojesMatehualaSan Luis PotosiC.P.78760Mexico Servicio de Anatomia Patologica Instituto Nacional de Cancerologia(INCan)Nino JesuisTlalpanCiudaddeMexicoC.P.14080Mexico Instituto de Salud Publica Universidad Veracruzana(UV)Av.Dr LuisDr.Castelazo Ayala s/nCol.Industrial AnimasXalapaVeracruzC.P.91190Mexico

Long non-coding RNAs(lncRNAs)are non-coding RNAs longer than 200 nucleotides with dynamic regulatory *** interact with a wide range of molecules such as dNA,RNA,and proteins to modulate diverse cellular functions through several mechanisms and,if deregulated,they can lead to cancer development and ***,it has been described that IncRNAs are susceptible to form gene fusions with mRNAs or other IncRNAs,breaking the paradigm of gene fusions consisting mainly of protein-coding ***,their biological significance in the tumor phenotype is still ***,their recent identification opens a new line of research to study their biological role in tumor-igenesis,and their potential as biomarkers with clinical relevance or as therapeutic *** present study aimed to review the IncRNA fusions identified so far and to know which of them have been associated with a potential *** address the current challenges to deepen their study as well as the reasons why they represent a future therapeutic window incancer.

关键词： Cancer Genefusions IncRNAs ncRNAs Therapy

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Lipid nanoparticles deliver mRNA to the blood-brain barrier

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Nano Research 2024年第10期17卷 9126-9134页

作者： Yanina Kuzminich Avraham Shakked Randi Calkins Sebastian Rudden Camille jones Jessie doan Bora Jang Elisa Schrader Echeverri Ryan Zenhausern Liming Lian david Loughrey Hannah E.Peck Rachelle Wiese dorothy Koveal Philip J.Santangelo James E.dahlman George C.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Parker H.Petit Institute for Bioengineering and Biosciences Georgia Institute of TechnologyAtlantaGA 30332USA Wallace H.Coulter department of Biomedical Engineering Emory University School of Medicine and Georgia Institute of TechnologyAtlantaGA 30332USA

Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous *** clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains *** we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted *** data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous *** the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.

关键词： lipid nanoparticle mRNA nanomedicine central nervous system blood-brain barrier

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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall david Hancock Tim Wallis Julian downward Rob M.Ewing donna E.davies Mark G.jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3d co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

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Foam rolling and stretching do not provide superior acute flexibility and stiffness improvements compared to any other warm-up intervention: A systematic review with meta-analysis

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Journal of Sport and Health Science 2024年第4期13卷 509-520页

作者： Konstantin Warneke Gerit Plöschberger Lars H.Lohmann Eric Lichtenstein daniel Jochum Stanislav d.Siegel Astrid Zech david G.Behm Institute of Sport Science University of KlagenfurtKlagenfurt am Wörthersee 9020Austria department of Human Motion Science and Exercise Physiology Friedrich Schiller UniversityJena 07749Germany department Sport Exercise and HealthUniversity of BaselBasel 4052Switzerland department of Health Sciences and Technology ETH ZurichZurich 8092Switzerland School of Human Kinetics and Recreation Memorial University of NewfoundlandSt.JohnsNL A1C 5S7Canada

Background:Acute improvement in range of motion(ROM)is a widely reported effect of stretching and foam rolling,which is commonly explained by changes in pain threshold and/or musculotendinous ***,these effects were also reported in response to various other active and passive interventions that induce responses such as enhanced muscle ***,we hypothesized that acute ROM enhancements could be induced by a wide variety of interventions other than stretching or foam rolling that promote an increase in muscle ***:After a systematic search in PubMed,Web of Science,and SPORTdiscus databases,38 studies comparing the effects of stretching and foam rolling with several other interventions on ROM and passive properties were *** studies had 1134 participants in total,and the data analysis resulted in 140 effect sizes(ESs).ES calculations were performed using robust variance estimation model with ***:Study quality of the included studies was classified as fair(PEdro score=4.58)with low to moderate certainty of *** showed no significant differences in ROM(ES=0.01,p=0.88),stiffness(ES=0.09,p=0.67),or passive peak torque(ES=-0.30,p=0.14)between stretching or foam rolling and the other identified *** plots revealed no publication ***:Based on current literature,our results challenge the established view on stretching and foam rolling as a recommended component of warm-up *** lack of significant difference between interventions suggests there is no need to emphasize stretching or foam rolling to induce acute ROM,passive peak torque increases,or stiffness reductions.

关键词： Range of motion Passive properties Muscletendon unit Muscle tissue

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A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： Pin Zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng Zhang Richard jones Binghe Xu department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer ***: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg Qd and 300 mg BId. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day *** samples were obtained on d 1 and d 28. Clinical responses were assessed every eight ***: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(dCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 ***: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

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A brief history of the Compendium of Physical Activities

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Journal of Sport and Health Science 2024年第1期13卷 3-5页

作者： Barbara E.Ainsworth Stephen d.Herrmann david R.Jacobs Jr. Melicia C.Whitt-Glover Catrine Tudor-Locke School of Exercise and Health Shanghai University of SportShanghai 200438China College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA Kansas Center for Metabolism and Obesity Research University of Kansas Medical CenterKansas CityKS 66160USA division of Epidemiology and Community Health University of MinnesotaMinneapolisMN 55455USA Gramercy Research Group KnightdaleNC 27545USA College of Health and Human Services University of North Carolina at CharlotteCharlotteNC 28223USA

The Compendium of Physical Activities(Compendium)was developed to address consistent assignment of physical activity(PA)intensity values used in PA epidemiology research of the association between PA and health outcomes.1The known protective effects of PA on incident health outcomes traces to the mid-1900s,with over 50 studies examining coronary heart disease(CHd)as the outcome of interest.

关键词： epidemiology Activities protective

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Simplified prediction models for acoustic installation effects of train-mounted equipment

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Railway Engineering Science 2024年第2期32卷 125-143页

作者： david Thompson dong Zhao Giacomo Squicciarini Institute of Sound and Vibration Research University of SouthamptonSouthampton SO171BJUK

Acoustic models of railway vehicles in standstill and pass-by conditions can be used as part of a virtual certification process for new *** each piece of auxiliary equipment,the sound power measured on a test bench is combined with meas-ured or predicted transfer *** is important,however,to allow for installation effects due to shielding by fairings or the train *** the current work,fast-running analytical models are developed to determine these installation *** model for roof-mounted sources takes account of diffraction at the corner of the train body or fairing,using a barrier *** equipment mounted under the train,the acoustic propagation from the sides of the source is based on free-field Green’s *** bottom surfaces are assumed to radiate initially into a cavity under the train,which is modelled with a simple diffuse field *** sound emitted from the gaps at the side of the cavity is then assumed to propagate to the receivers according to free-field Green’s *** show good agreement with a 2.5d boundary element model and with *** uncertainty and parametric uncertainty are *** largest variability occurs due to the height and impedance of the ground,especially for a low *** leads to standard deviations of up to 4 dB at low *** the roof-mounted sources,uncertainty over the location of the corner used in the equivalent barrier model can also lead to large standard deviations.

关键词： Train noise Auxiliary equipment Acoustic installation effects Virtual certification Uncertainty

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